rs574130239
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2PP2BP4_Moderate
The NM_000834.5(GRIN2B):āc.3043T>Gā(p.Ser1015Ala) variant causes a missense change. The variant allele was found at a frequency of 0.00000658 in 152,020 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S1015T) has been classified as Likely benign.
Frequency
Consequence
NM_000834.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GRIN2B | NM_000834.5 | c.3043T>G | p.Ser1015Ala | missense_variant | 14/14 | ENST00000609686.4 | |
GRIN2B | NM_001413992.1 | c.3043T>G | p.Ser1015Ala | missense_variant | 15/15 | ||
GRIN2B | XM_005253351.3 | c.829T>G | p.Ser277Ala | missense_variant | 4/4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GRIN2B | ENST00000609686.4 | c.3043T>G | p.Ser1015Ala | missense_variant | 14/14 | 1 | NM_000834.5 | P1 | |
GRIN2B | ENST00000637214.1 | c.69+44408T>G | intron_variant | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.00000658 AC: 1AN: 152020Hom.: 0 Cov.: 33
GnomAD4 exome Cov.: 37
GnomAD4 genome ? AF: 0.00000658 AC: 1AN: 152020Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1AN XY: 74246
ClinVar
Submissions by phenotype
not provided Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jun 01, 2024 | GRIN2B: PM2, PP2, BP4 - |
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Jul 20, 2022 | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
Intellectual disability, autosomal dominant 6;C4015316:Developmental and epileptic encephalopathy, 27 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 25, 2021 | This sequence change replaces serine with alanine at codon 1015 of the GRIN2B protein (p.Ser1015Ala). The serine residue is weakly conserved and there is a moderate physicochemical difference between serine and alanine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with GRIN2B-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at